Intentional limited operation for minute peripheral adenocarcinoma of the lung

The purpose of this report is to evaluate the limited operation for peripheral minute adenocarcinoma of the lung. Firstly, 44 cases (47 lesions) of surgically resected minute peripheral lung adenocarcinoma, 10 mm or less in diameter, were reviewed using Noguchi's classification, and the correlation between high resolution CT (HRCT) images and the clinicopathological features was examined retrospectively. All type A and B adenocarcinomas (n = 14) had no recurrence and all cases were the air containing type by HRCT. Lymph node metastasis and lymphatic/vascular involvement were detected with type C, D, E, F and 3 cases among them were died for recurrence. Based on those results, from April 2000, intentional limited operation was prospectively performed for 14 patients (16 lesions) with peripheral nodule showing ground-glass opacity on HRCT. The pathological findings were type A (n = 9), type B (n = 5), and atypical adenomatous hyperplasia was one case (If the findings were confirmed type C, D, E, F by permanent section diagnosis, VATS lobectomy will be performed). We recommend limited operation should be performed in only type A or B adenocarcinoma and permanent section diagnosis is necessary to determine whether or not.     

Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung

BACKGROUND: Macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine and glucocorticoid-induced immunomodulator as well as a regulator of tumor growth. Although positive and negative effects of MIF on tumor cell growth have been reported, to the authors' knowledge the precise role of MIF in tumorigenesis remains unclear. In the current study the authors assessed expression of MIF protein and mRNA in lung adenocarcinomas with regard to patient prognosis. METHODS: Immunohistochemical analysis was performed on tissue specimens surgically obtained from 74 patients with primary lung adenocarcinoma (American Joint Committee on Cancer pathologic Stages I, II, and IIIa). In addition, expression of MIF mRNA in the cancerous tissue was investigated using in situ hybridization. Patient prognosis was evaluated with regard to MIF expression levels and its distribution was analyzed with the Kaplan-Meier method. RESULTS: MIF mRNA and MIF protein were observed in the bronchial epithelium, alveolar epithelium, vascular smooth muscle, and alveolar macrophages in the normal lung tissue. In tumor tissue from lung adenocarcinoma specimens, both MIF mRNA and protein were observed at much higher levels than in the normal alveolar epithelium. MIF protein was observed diffusely in the cytoplasm of tumor cells in all tumor specimens examined. MIF protein also was observed in the nuclei of tumor cells from 59 patients (79.7%), whereas it was not observed in the nuclei of tumor cells from 15 patients (20.3%). The patients without nuclear MIF expression had a worse prognosis compared with those patients with MIF expression in the nuclei (P = 0.04). CONCLUSIONS: The results of the current study suggest that intracellular MIF distribution predicts patient prognosis in individuals with adenocarcinoma of the lung.     

People's functional evaluations, perception of fairness, and commitment to the state

A questionnaire was mailed to a random sample of 3,000 people who were older than 20, and 993 responded. The questionnaire was designed to measure the respondent's functional evaluations of Japan's political branches (the Diet, the Government, and its administrative agencies), its perceived fairness, his/her emotional and utilitarian commitment to Japan, and the political party he/she supported. Based on the fairness-bond theory model, we hypothesized that positive evaluations of political branches would increase perceived fairness, which in turn leaded to a stronger commitment. Path analysis indicated that the hypothesis was partially supported, and that functional evaluations of political branches had a direct effect on the commitment. It was also found that politically conservative respondents showed more positive evaluations and stronger commitment to Japan than liberal ones, suggesting political attitudes as a moderator variable for the fairness mediation.     

Lobectomy: Video-Assisted thoracic surgery versus posterolateral thoracotomy

Background:Video-assisted lobectomy has been adopted by many thoracic surgeons, because it is a less invasive approach to small peripheral lung cancers. However, some authors disagree that video-assisted lobectomy is less invasive than traditional thoracotomy and lobectomy. The purpose of this study was to evaluate the advantages of video-assisted lobectomy over posterolateral thoracotomy and lobectomy in terms of pain-related morbidity. Methods: A total of 70 patients with clinical T1N0M0 non-small-cell lung carcinomas underwent lobectomy with complete mediastinal lymphadenectomy. Of these 35 underwent posterolateral thoracotomy (between April 1994 and December 1995; open group), and 35 underwent video-assisted thoracic surgery (VATS) (between January and December 1996; VATS group). Results: Although the operative time was significantly longer in the VATS group (p=0.04), the intraoperative blood loss was significantly less (p=0.03). No significant differences were found for the two groups with respect to the total number of mediastinal lymph nodes dissected or duration of chest tube drainage. Postoperative pain was less severe as determined by the number of doses of analgesics required between postoperative days 0 and 7 (p<0.0001), and the length of postoperative hospitalization was shorter in the VATS group (p<0.0001). Conclusion: Video-assisted lobectomy is associated with decreased postoperative pain and shortened length of postoperative hospitalization, when compared with posterolateral thoracotomy and lobectomy.     

The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin‐like protease(s) in a subpopulation of microglia in neonatal rat brain

To differentiate subtypes of microglia (MG), we developed a novel monoclonal antibody, 9F5, against one subtype (type 1) of rat primary MG. The 9F5 showed high selectivity for this cell type in Western blot and immunocytochemical analyses and no cross‐reaction with rat peritoneal macrophages (Mφ). We identified the antigen molecule for 9F5: the 50‐ to 70‐kDa fragments of rat glycoprotein nonmetastatic melanoma protein B (GPNMB)/osteoactivin, which started at Lys¹⁷⁰. In addition, 9F5 immunoreactivity with GPNMB depended on the activity of furin‐like protease(s). More important, rat type 1 MG expressed the GPNMB fragments, but type 2 MG and Mφ did not, although all these cells expressed mRNA and the full‐length protein for GPNMB. These results suggest that 9F5 reactivity with MG depends greatly on cleavage of GPNMB and that type 1 MG, in contrast to type 2 MG and Mφ, may have furin‐like protease(s) for GPNMB cleavage. In neonatal rat brain, amoeboid 9F5+ MG were observed in specific brain areas including forebrain subventricular zone, corpus callosum, and retina. Double‐immunοstaining with 9F5 antibody and anti‐Iba1 antibody, which reacts with MG throughout the CNS, revealed that 9F5+ MG were a portion of Iba1+ MG, suggesting that MG subtype(s) exist in vivo. We propose that 9F5 is a useful tool to discriminate between rat type 1 MG and other subtypes of MG/Mφ and to reveal the role of the GPNMB fragments during developing brain. GLIA 2016;64:1938–1961     

Oral administration of the extract from Hatakeshimeji (Lyophyllum decastes sing.) mushroom inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

We examined whether the extract from Hatakeshimeji (Lyophyllum decastes, LD) mushrooms suppresses the development of atopic dermatitis (AD)-like skin lesions induced by repeated application of picryl chloride (PiCl) in NC/Nga mice. Oral administration of LD extract to NC/Nga mice inhibited the development of AD-like skin lesions based on lower total skin severity scores and serum immunoglobulin E (IgE) levels. Splenic lymphocytes were stimulated with the T cell mitogen concanavalin A, and secretion of a Th1 cytokine (IFN-gamma) and a Th2 cytokine (IL-4) was determined by ELISA. IFN-gamma production was not inhibited by treatment with LD extract. On the other hand, IL-4 production was significantly decreased by treatment with LD extract. These results suggest that LD extract exerts anti-allergic actions by suppressing the serum IgE and Th2-type immune responses.     

Rare variant of persistent primitive hypoglossal artery, arising from the external carotid artery

A 63-year-old man presented with an extremely rare variant of persistent primitive hypoglossal artery (PHA), which was found incidentally during examination for a contralateral asymptomatic internal carotid artery (ICA) stenosis. This anastomotic vessel arose from the external carotid artery, not the ICA, and joined the vertebrobasilar artery through the hypoglossal canal. Persistent PHA is rare and the reported incidence is 0.027-0.26%. Recognition of the existence of this variant vessel and preservation during neuroradiologic intervention or surgery is important to prevent possible ischemic complications.     

Identification of herbal components as TRPA1 agonists and TRPM8 antagonists

Transient receptor potential (TRP) channels are non-selective cation channels that are implicated in analgesia, bowel motility, wound healing, thermoregulation, vasodilation and voiding dysfunction. Many natural products have been reported to affect the activity of TRP channels. We hypothesize that numerous traditional herbal medicines (THMs) might exert their pharmacological activity through modulating the activity of TRP channels. The present study aimed to evaluate the effects of flavonoid aglycones and their glycosides, which are the main components of many THMs, on the TRP channel subtypes. A Ca²⁺ influx assay was performed using recombinant human TRPA1, TRPV1, TRPV4 and TRPM8 cell lines. Our findings showed that flavonoid aglycones and glycycoumarin activated TRPA1. In particular, isoflavone and chalcone compounds displayed potent TRPA1 agonistic activity. Furthermore, flavone aglycones showed concomitant potent TRPM8 inhibiting activity. Indeed, flavone, isoflavone aglycones, non-prenylated chalcones and glycycoumarin were found to be TRPM8 inhibitors. Hence, flavonoid aglycones metabolized by lactase-phlorizin hydrolase and β-glucosidase in the small intestine or gut microbiota of the large intestine could generate TRPA1 agonists and TRPM8 antagonists.

     

Murine Cyp3a knockout chimeric mice with humanized liver: prediction of the metabolic profile of nefazodone in humans

Chimeric mice with humanized livers (PXB mice) are used to investigate the metabolism and pharmacokinetics of drugs in humans. However, residual murine enzymatic activities derived from the liver and the presence of mouse small intestinal metabolism can hamper the prediction of human drug metabolism. Recently murine Cytochrome P450 3a gene knockout chimeric mice with humanized livers (Cyp3a KO CM) were developed. To evaluate the prediction of drug metabolism, nefazodone (NEF) was administered orally at 10 mg/kg to the following mouse strains: Cyp3a KO CM, murine Cyp3a gene knockout (Cyp3a KO), PXB and severe combined immunodeficiency (SCID) mice. Liquid chromatography‐mass spectrometry was used for metabolic profiling of plasma, urine and bile. The prediction of human metabolite levels such as hydroxy nefazodone (OH‐NEF), triazoledione form (TD), m‐chlorophenylpiperazine and dealkyl metabolites in Cyp3a KO CM was superior to that in Cyp3a KO, PXB or SCID mice. Further, clinical exposure levels of NEF, OH‐NEF and TD were reproduced in Cyp3a KO CM. In contrast, NEF was rapidly metabolized to TD in both PXB and SCID mice but not in Cyp3a KO mice, suggesting that murine CYP3A is involved in the elimination of NEF in these mice. These findings demonstrate that the metabolic profile of NEF in Cyp3a KO CM differs qualitatively and quantitatively from that in PXB mice due to the higher metabolic rate of NEF and its metabolites via murine CYP3A. Therefore Cyp3a KO CM might be useful in predicting the metabolic profiles of drug candidates in humans. Copyright © 2016 John Wiley & Sons, Ltd.     

Accelerated reoxygenation of a murine fibrosarcoma after carbon-ion radiation.

PURPOSE: Reoxygenation of a murine tumour after irradiation with carbon ions was investigated and compared to that after gamma-rays. MATERIALS AND METHODS: NFSa fibrosarcoma cells were transplanted into the right hind legs of syngeneic C3H male mice. Conditioning irradiation with either 290 MeV/u carbon ions or 137-Cs gamma-rays was delivered to the tumours at 8 mm diameter. At given times after irradiation the leg tumours, either clamped or not, received test doses of photons. Differences in tumour growth delay between the clamped and non-clamped tumours were interpreted in terms of reoxygenation. A lung-colony assay was used to obtain cell-survival curves. RESULTS: The oxygen enhancement ratio in the NFSa tumour for 74 keV microm(-1) carbon ions was 1.6 while that for gamma-rays was 3.4. The NFSa tumours reoxygenated 4 days after 30 Gy of gamma-ray irradiation, but reoxygenated as early as 1 day after 16 Gy of carbon ions. Reoxygenation after gamma-rays shortened to 1 day when the tumours were initially clamped for the conditioning irradiation. CONCLUSIONS: The fraction of surviving oxic cells in the NFSa tumours is larger after irradiation with carbon ions than with gamma-rays, resulting in accelerated reoxygenation.